Tetrabutylammonium Fluoride → (5S,6S,9R)-6-(2,3-difluorophenyl)-9-hydroxy-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-5-yl acetate

Participants

Reaction Steps

In a 100 mL round-bottom flask was dissolved (5S,6S,9R)-6-(2,3-difluorophenyl)-9-(triisopropylsilyloxy)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-5-yl acetate (1098 mg, 2.243 mmol) (azeotroped with dry benzene) in tetrahydrofuran (20 mL) to give a colorless solution. TBAF (2.69 mL, 2.69 mmol) was added, and the resulting light yellow solution was stirred at room temperature for 2 h (8:30 am). LCMS indicated complete conversion. Tetrahydrofuran was removed in vacuo and the residue was diluted with water and ethyl acetate. The layers were separated. The organic layer was washed with brine, dried, and concentrated to give a colorless oil. Purification by FCC up to 70% ethyl acetate/hexane afforded the desired product (648 mg, 87% for 2 steps) as a colorless oil. MS(ESI)[M+H+]=334.21; 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.47 (dd, J=4.78, 1.51 Hz, 1H) 7.69 (d, J=7.30 Hz, 1H) 7.28 (dd, J=7.81, 5.04 Hz, 1H) 6.94-7.10 (m, 3H) 6.20 (d, J=10.32 Hz, 1H) 5.95 (br. s., 1H) 4.95 (dd, J=11.21, 1.64 Hz, 1H) 3.16-3.31 (m, 1H) 2.27-2.41 (m, 2H) 2.06-2.19 (m, 1H) 1.80 (s, 3H) 1.48-1.63 (m, 1H); 13C NMR (101 MHz, CHLOROFORM-d) δ ppm 168.96 (s, 1C) 157.96 (s, 1C) 149.66-151.75 (d, J=12.6 and 199 Hz, 1C) 147.21-149.29 (d, J=13 and 198 Hz, 1C) 146.00 (s, 2C) 133.43 (s, 1C) 132.23 (d, J=11.56 Hz, 1C) 131.99 (s, 2C) 123.90-124.24 (m, 2C) 122.89 (br. s., 1C) 122.66 (s, 2C) 115.36 (d, J=16.95 Hz, 2C) 72.77 (s, 2C) 71.14 (s, 3C) 42.12 (br. s., 1C) 35.66 (s, 2C) 32.68 (s, 2C) 20.28 (s, 2C); 19F NMR (376 MHz, CHLOROFORM-d) δ ppm −138.20-−137.93 (m, 1F) −143.38-−143.16 (m, 1F).

Provenance & Evidence